Combining cerebrospinal fluid and PI‐2620 tau‐PET for biomarker‐based stratification of Alzheimer's disease and 4R‐tauopathies

Abstract

INTRODUCTION

Recent advances in biomarker research have improved the diagnosis and monitoring of Alzheimer's disease (AD), but in vivo biomarker-based workflows to assess 4R-tauopathy (4RT) patients are currently missing. We suggest a novel biomarker-based algorithm to characterize AD and 4RTs.

METHODS

We cross-sectionally assessed combinations of cerebrospinal fluid measures (CSF p-tau181 and t-tau) and 18F-PI-2620 tau-positron emission tomography (PET) in patients with AD (n = 64), clinically suspected 4RTs (progressive supranuclear palsy or corticobasal syndrome, n = 82) and healthy controls (n = 19).

RESULTS

Elevated CSF p-tau181 and cortical 18F-PI-2620 binding was characteristic for AD while normal CSF p-tau181 with elevated subcortical 18F-PI-2620 binding was characteristic for 4RTs. 18F-PI-2620-assessed posterior cortical hypoperfusion could be used as an additional neuronal injury biomarker in AD.

DISCUSSION

The specific combination of CSF markers and 18F-PI-2620 tau-PET in disease-specific regions facilitates the biomarker-guided stratification of AD and 4RTs. This has implications for biomarker-aided diagnostic workflows and the advancement in clinical trials.

Highlights

Novel biomarker-based algorithm for differentiating AD and 4R-tauopathies.

A combination of CSF p-tau181 and 18F-PI-2620 discriminates AD versus 4R tauopathies.

Hypoperfusion serves as an additional neuronal injury biomarker in AD.

Metadata

Item Type:	Article
Authors/Creators:	Dilcher, R. https://orcid.org/0000-0002-1307-6747 Wall, S. Groß, M. Katzdobler, S. Wagemann, O. Palleis, C. Weidinger, E. Fietzek, U. Bernhardt, A. Kurz, C. Ferschmann, C. Scheifele, M. Zaganjori, M. Gnörich, J. Bürger, K. Janowitz, D. Rauchmann, B. Stöcklein, S. Bartenstein, P. Villemagne, V. Seibyl, J. Sabri, O. Barthel, H. Perneczky, R. https://orcid.org/0000-0003-1981-7435 Schöberl, F. Zwergal, A. Höglinger, G.U. Levin, J. Franzmeier, N. https://orcid.org/0000-0001-9736-2283 Brendel, M.
Copyright, Publisher and Additional Information:	© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords:	18F‐PI‐2620; 4‐repeat tauopathies; Alzheimer's disease; PET; biomarkers; cerebrospinal fluid; perfusion; tau
Dates:	Published: October 2024 Published (online): 12 September 2024 Accepted: 8 July 2024
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Depositing User:	Symplectic Sheffield
Date Deposited:	15 Oct 2024 15:12
Last Modified:	25 Feb 2025 12:32
Status:	Published
Publisher:	Wiley
Refereed:	Yes
Identification Number:	10.1002/alz.14185
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:218282

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Combining cerebrospinal fluid and PI‐2620 tau‐PET for biomarker‐based stratification of Alzheimer's disease and 4R‐tauopathies

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